ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1616C>T (p.Thr539Met) (rs80357374)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000225759 SCV000075555 benign Hereditary breast and ovarian cancer syndrome 2018-01-03 criteria provided, single submitter clinical testing
GeneDx RCV000120282 SCV000209930 likely benign not specified 2017-11-20 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000162708 SCV000213169 likely benign Hereditary cancer-predisposing syndrome 2018-01-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Co-occurence with mutation in same gene (phase unknown),Other strong data supporting benign classification
Counsyl RCV000111655 SCV000488835 uncertain significance Breast-ovarian cancer, familial 1 2016-06-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000225759 SCV000494410 benign Hereditary breast and ovarian cancer syndrome 2016-03-17 criteria provided, single submitter clinical testing Variant Summary: The variant of interest causes a misense change involving a non-conserved nucleotide with 3/4 in silico programs (SNPs&GO not captured here due to low reliability index) predict a "benign" outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 11/120938 (1/10993), predominantly in the South Asian cohort, 9/16496 (1/1832), which does not exceed the predicted maximum expected allele frequency for a pathogenic BRCA1 variant of 1/1000. The variant of interest has been reported in multiple affected individuals via publications and databases, which indicate the variant to co-occur with pathogenic BRCA1 variants, c.1687C>T (p.Gln563X - scored DV) and c.5030_5033delCTAA (p.Thr1677IlefsX2 - scored DV) and 3 different BRCA2 variants, c.2808_2811delACAA(p.Lys936_Gln937?fs) c.6037A>T (p.Lys2013Ter) and c.3975_3978dupTGCT (p.Ala1327fsX4), indicating a benign role. In addition, multiple reputable clinical laboratories cite the variant as "likely benign." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000120282 SCV000600259 likely benign not specified 2016-09-11 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586975 SCV000698878 benign not provided 2016-03-17 criteria provided, single submitter clinical testing Variant Summary: The variant of interest causes a misense change involving a non-conserved nucleotide with 3/4 in silico programs (SNPs&GO not captured here due to low reliability index) predict a "benign" outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 11/120938 (1/10993), predominantly in the South Asian cohort, 9/16496 (1/1832), which does not exceed the predicted maximum expected allele frequency for a pathogenic BRCA1 variant of 1/1000. The variant of interest has been reported in multiple affected individuals via publications and databases, which indicate the variant to co-occur with pathogenic BRCA1 variants, c.1687C>T (p.Gln563X - classified as pathogenic by LCA) and c.5030_5033delCTAA (p.Thr1677IlefsX2 - classified as pathogenic by LCA) and 3 different BRCA2 variants, c.2808_2811delACAA(p.Lys936_Gln937?fs) c.6037A>T (p.Lys2013Ter) and c.3975_3978dupTGCT (p.Ala1327fsX4), indicating a benign role. In addition, multiple reputable clinical laboratories cite the variant as "likely benign." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Benign.
Color RCV000162708 SCV000910914 benign Hereditary cancer-predisposing syndrome 2016-11-14 criteria provided, single submitter clinical testing
ITMI RCV000120282 SCV000084434 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA1) RCV000111655 SCV000144144 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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